Studies were performed in three groups of anesthetized dogs to compare the structurally related peptides atrial natriuretic peptide (ANP) and C-type natriuretic peptide (CNP). Group 1 (n = 5) and group 2 (n = 4) received intravenous infusions of CNP or ANP respectively at doses of 10 ng.kg-1.min-1 and 100 ng.kg-1.min-1. Group 3 (n = 5) received CNP intrarenally at doses of 1 ng.kg-1.min-1 and 5 ng.kg-1.min-1. Intravenous infusion of CNP resulted in a greater decrease in blood pressure when compared with ANP. This marked decrease in blood pressure observed with CNP was associated with a significantly smaller increase in guanosine 3',5'-cyclic monophosphate (cGMP). In contrast, neither intravenous nor intrarenal administration of CNP was associated with natriuresis as observed with ANP. The current study also demonstrates the presence of CNP immunoreactivity in canine plasma at low picomolar concentrations. Further characterization by gel permeation chromatography demonstrated that circulating CNP immunoreactivity corresponds to the 22-amino acid form of the peptide. In conclusion, this study demonstrates that CNP circulates in low picomolar concentrations and is potently vasoactive in vivo, suggesting a potential role in the regulation of vascular tone.